Alström (pronounced Al-strom) syndrome is part of larger group of disorders known as rare genetic disorders of obesity.
What causes Alström syndrome?
Alström syndrome is caused by genetic variants genetic variants Changes (also known as variants) in the standard “spelling” of a gene. Gene variants can result in serious health problems or be “silent” with no negative health effects. , or changes, in the ALMS1 gene genes Our body’s instruction manual that informs how our bodies grow, develop, and function. It is through our genes that traits are passed down from parent to offspring. . These changes disrupt signals signals Chemicals and proteins that the body and brain use to communicate and direct processes in the body. in the melanocortin-4 receptor (MC4R) pathway MC4R pathway The MC4R pathway is one of the pathways that regulates weight and appetite in the brain. Click here to learn more about the MC4R pathway. . The MC4R pathway is an important pathway in the brain that helps tell your body when you are hungry and when you are full. The ALMS1 gene provides instructions for making a protein that is not fully understood, but scientists believe that this protein plays an important role in the maintenance and function of microscopic cilia. Cilia are tiny finger-like protrusions that allow our cells to move from one place to another, and help us see, hear, and smell.
What are the key clinical features of Alström syndrome?
It is important to remember that the symptoms of Alström syndrome can develop at different times for different people. Not all people have the same symptoms. In fact, symptoms can vary even among siblings.
You don’t have to have all of the symptoms on the list below in order to be diagnosed with Alström syndrome. The main signs and symptoms of Alström syndrome include:
- Poor vision (cone-rod dystrophy cone-rod dystrophy A condition that causes light-sensing cells in the retina (the back part of the eye) to not work properly, leading to progressive vision loss. )
- Sensitivity to light (photophobia photophobia Increased sensitivity to light. )
- Uncontrolled movement of the eye (nystagmus nystagmus Uncontrolled movements of the eye. )
- Severe, early-onset obesity (<1-year-old)
- Insatiable hunger
- Short stature
- Progressive hearing loss (before age 10)
- Abnormal hormone hormone Chemical messengers made in the endocrine glands that control body functions. levels (endocrine abnormalities endocrine abnormalities The endocrine system is made of organs, glands, and hormones that tell the body how to do its job. This system influences how your heart beats, how you use the food you eat, how you grow, and many other important body functions. An endocrine abnormality means that one or more parts of the system is not working the way it should. such as insulin resistance)
- Dilated heart muscle (cardiomyopathy cardiomyopathy A condition where the heart is abnormally enlarged, which compromises its ability to pump blood to the rest of the body. )
- Liver disease
- Progressive kidney disease
Additional signs and symptoms
Babies with Alström syndrome are typically of average weight at birth, but begin to rapidly gain weight within the first weeks of life. Weight gain usually continues into adult life, though some people might see their weight normalize after their teenage years. Almost 98% of teenagers with Alström syndrome are in the 5th percentile or less for height.
Children and teenagers may also experience hearing loss, an enlarged heart, liver, or spleen, insulin resistance syndrome, type 2 diabetes, and end-stage renal disease (ESRD).
How is Alström syndrome inherited?
Alström syndrome is inherited in an autosomal recessive autosomal recessive Autosomal recessive (AR) conditions occur when a person inherits two non-working copies of a disease-causing (pathogenic) gene variant from their parents. manner. This means that someone with Alström syndrome will have two copies of the genetic variant that causes the disorder. You can only inherit an autosomal recessive disorder if both of your parents are “carriers carrier In an autosomal recessive inheritance pattern, if an individual inherits one normal copy of a gene and one copy of a disease-causing variant, they are called a carrier and will generally not have any symptoms of the disease that variant causes. ” for that disorder, meaning that they both carry one copy with the genetic variant and one copy without it.
How is Alström syndrome diagnosed?
Like many rare genetic disorders of obesity, Alström syndrome can be diagnosed on the basis of clinical findings. If Alström syndrome is clinically suspected, a blood test can be ordered for genetic testing to help confirm the diagnosis.